The present invention relates to methods and compositions for preventing, treating or controlling helmintic, arthropod ectoparasitic and acaridal infections in warm-blooded animals by administering thereto an effective amount of the agents (compounds) designated LL-F28249.alpha., .beta., .gamma., .delta., .epsilon., .xi., .eta., .iota., .kappa., .lambda., .mu., .nu. and .omega., or mixtures thereof, such as the fermentation broth, or whole mash or the pharmaceutically and pharmacologically-acceptable salts thereof. Plant nematodes also are effectively controlled by use of these agents, mixtures and/or salts. Further, these agents are effective as insecticidal agents, as well.
The diseases described above cause not only devastating effects but also serious economic problems and losses for farmers raising meat-producing animals such as swine, sheep, cattle, goats, rabbits, and poultry. Further, such diseases are a source of great concern for companion animals such as horses, dogs and cats. Although these diseases have been recognized for many years and drugs exist for the treatment and/or prevention of such diseases, the present invention utilizes an entirely new set of active agents, isolated from a previously unknown microorganism, for the prevention, treatment or control of those diseases.
For instance, U.S. Pat. No. 3,950,360, Aoki et al, Apr. 13, 1976, discloses certain antibiotic substances obtained by culturing a Streptomyces microorganism, said compounds being useful as insecticides and acaracides. But as seen from the characteristics identifying such microorganism, the present microorganism is distinct, and its active components are derived from totally different microorganisms. Further, an entire series of U.S. patents relates to certain compounds produced by the fermentation of Streptomyces avermitilis, a distinct organism from the present one (U.S. Pat. No. 4,171,314, Chabala et al, Oct. 16, 1979; U.S. Pat. No. 4,199,569, Chabala et al, Apr. 22, 1980; U.S. Pat. No. 4,206,205, Mrozik et al, Jun. 3, 1980; U.S. Pat. No. 4,310,519, Albers-Schonberg, Jan. 12, 1982; U.S. Pat. No. 4,333,925, Buhs et al, Jun. 8, 1982). U.S. Pat. No. 4,423,209, Mrozik, Dec. 27, 1983 relates to the process of converting some of these less desirable components to more preferred ones. However, the present active agents identified as LL-F28249.alpha., .beta., .gamma., .delta., .epsilon., .xi., .eta., .theta., .iota., .delta., .lambda., .mu., .nu. and .omega., are derived from the fermentation of a newly discovered and previously uncultivated microorganism. Also, the present compounds and/or the fermentation broth or whole mash of microorganism Streptomyces cyaneogriseus ssp. noncyanogenus NRRL 15773, plus the pharmaceutically and pharmacologically-acceptable salts thereof (collectively referred to as active ingredient), exhibit excellent and effective treatments and/or prevention of these serious diseases of warm-blooded animals.
The full name of the microorganism LL-F28249, NRRL No. 15773, in terms of genus, species, and subspecies is Streptomyces cyaneogriseus noncyanogenus; however, for brevity it is referred to as above written throughout the specification and claims.
The strain is assigned to the genus Streptomyces based upon morphology and cell chemistry (content of the L isomer of diaminopimelic acid). The strain's morphology and physiological data place it close to S. cyaneogriseus, as represented by ISP 5534 (ATCC 27426) . Then, comparisons of the formation of gray aerial mycelium soluble pigments on media (Table A) and coiled chains of smooth conidia (3-25 spores per chain) were made. The present strain is negative for blue soluble pigment wherein the comparison strain, ISR 5534, is positive. The strains have similar reactions in the ISP carbohydrate utilization tests indicating positive for arabinose, fructose, glucose, rhamnose and xylose, while indicating negative for inositol, mannitol, raffinose and sucrose (ISP 5534 slightly positive). However, the strains differ in several characters (Table B) out of 53 in the Gordon tests. These differences support the creation of a subspecies of S. cyaneogenseus for the present microorganism.
TABLE A ______________________________________ Comparison of F 28249 and ISP 5534 on ISP Morphology Test Media (Numbers are from NBS-ISCC) Medium F 28249 ISP 5534 ______________________________________ Yeast-Malt .sup. A.m..sup.1 Medium gray Light to medium (ISP 2) (265) gray (264-265) V.m. Light tannish (75) Light tannish-white Deep yellow-brown to blackish-blue (188) S.p. Light brown Light brown Inorganic A.m. Light olive-gray Medium gray (265) salts (112 to medium gray starch (265 (ISP 4) V.m. Deep gray to black Gray-purplish-blue (266-267) (204) S.p. Grayish-yellowish- None brown Glycerol- A.m. 263 (white) to 263 (white) to Asparagine yellowish-gray (93) light gray (264) (ISP 5) V.m. Black (267) to light Gray-purplish-blue olive brown (96) (203-204) S.p. Slight brownish Light yellowish- gray Oatmeal A.m. Yellow-gray (93) None (ISP 3) V.m. Colorless Colorless S.p. Slight yellowish None ______________________________________ .sup.1 = A.m., aerial mycelium; V.m. = vegetative mycelium; S.p. = Soluble pigment
TABLE B ______________________________________ Comparison of Lederle F 28249 with ISP 5534 (Gordon Tests) F28249 ISP 5534 ______________________________________ Growth on/at Salicin .+-. - 10.degree. - + 45.degree. + - Production of + - Urease Decarboxylation of - + Mucate Acid Production Raffinose - + Sucrose - + ______________________________________ Both strains have the following reactions: Positive Hydrolysis of casein, hypoxanthine, xanthine, tyrosine, adrenine, potato starch, gelatin, and esculin; Production of phosphatase Sensitivity to lysozyme Decarboxylation of acetate, citrate, lactate, malate, oxalate and propionate Acid production from arabinose, cellobiose, dextrin, fructose, galactose, glucose, glycerol, lactose, maltose, mannose, .alpha.-methyl Dglucoside, rhamnose, salicin, trehalose. Negative Production of nitrate reductase Decarboxylation of benzoate and tartrate Acid from adonitol, dulcitol, erythritol, inositol, mannitol, sorbitol, .beta.-methylD-xyloside. Growth on 5% NaCl